78 articles - From Friday Jun 03 2022 to Friday Jun 10 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Blood |
The International Consensus Classification of Mature Lymphoid Neoplasms: A Report from the Clinical Advisory Committee. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification (ICC) of mature lymphoid, histiocytic, and dendritic cell tumors. |
meta-analyses and systematic reviews
RCT, clinical trials, retrospective studies, etc…
| Ann Oncol |
Pembrolizumab in Microsatellite Instability High or Mismatch Repair Deficient Cancers: Updated Analysis from the Phase 2 KEYNOTE-158 Study. Pembrolizumab demonstrated clinically meaningful and durable benefit, with high ORR of 30.8%, long median duration of response of 47.5 months, and manageable safety across a range of heavily pretreated, advanced MSI-H/dMMR noncolorectal cancers, providing support for use of pembrolizumab in this setting. |
| Blood |
Anticoagulation in Hospitalized Patients with COVID-19. Three randomized control trials suggesting benefit of therapeutic heparin in hospitalized non-critically ill patients with COVID-19 have led to conditional guideline recommendations for this treatment. By contrast, prophylactic dose heparin is recommended for critically ill patients. Unprecedented collaboration and rapidly funded research has improved care of hospitalized patients with COVID-19. |
Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma. The ORR and CR rate were 49.9% and 29.9% in SCHOLAR-5 compared to 94.2% and 79.1% in ZUMA-5, for odds ratios of 16.2 (95%CI: 5.6-46.9) and 8.9 (95%CI: 4.3-18.3). Compared to available therapies, axi-cel demonstrated an improvement in meaningful clinical endpoints. This study suggests axi-cel may address an important unmet need for r/r FL patients. |
Hemolysis, free hemoglobin toxicity and scavenger protein therapeutics. Pathological hemolysis outpaces macrophage capacity and scavenger synthesis across a diversity of diseases. This imbalance leads to hemoglobin-driven disease progression. To meet a void in treatment options, scavenger protein-based therapeutics are in clinical development. |
How I Treat Immune Mediated Thrombotic Thrombocytopenic Purpura After Hospital Discharge. There is both the risk of relapse and long-term complications that include neurocognitive deficits and cardiovascular events in remission that occur in patients after recovery from an acute iTTP episode. Data on the risk factors for the development of these complications, the appropriate screening, and treatment of these complications is limited due to the paucity of research. In this article, we review the current understanding on the risk factors for exacerbation, relapse, and long-term complications of iTTP, and discuss our approach in following iTTP patients after hospital discharge and during the long-term follow-up in the outpatient setting. |
IL-1b expression in bone marrow dendritic cells is induced by TLR2 agonists and regulates HSC function. Single cell RNA sequencing of low risk MDS bone marrow show that IL1B and TLR1 expression is increased in DCs. Collectively, these data suggest a model in which TLR1/2 stimulation of DCs induces secretion of IL-1b and other inflammatory cytokines into the perivascular niche, which in turn, regulates multipotent HSPCs. Increased DC TLR1/2 signaling may contribute to altered HSPC function in MDS by increasing local IL-1b expression. |
Outcomes Following Treatment for Adenosine Deaminase Deficient Severe Combined Immunodeficiency: A Report from the PIDTC. Five-year EFS (90.5%) and OS (100%) were best for matched sibling and matched family donors (MSD/MFD). For patients treated after the year 2000 and without active infection at the time of FDCT, no difference in 5-year EFS or OS was found between HCT using a variety of transplant approaches and ERT-GT. This suggests alternative donor HCT may be considered when MSD/MFD HCT and GT are not available, particularly when newborn screening identifies ADA-SCID patients soon after birth and before the onset of infections. |
p57Kip2 regulates embryonic blood stem cells by controlling sympathoadrenal progenitor expansion. To gain further molecular insights, we have generated a single-cell RNA-Seq dataset of al Ngfr+ sympathoadrenal cells around the dorsal aorta to dissect their differentiation pathway. Importantly, this not only defined the relevant p57Kip2-expressing SNS progenitor stage, but also revealed that some neural crest cells, upon arrival at the aorta, are able to take an alternative differentiation pathway, giving rise to a subset of ventrally restricted mesenchymal cells that express important HSC-supportive factors. Neural crest cells thus appear to contribute to the AGM HSC niche via two different mechanisms: SNS-mediated catecholamine secretion and HSC-supportive mesenchymal cell production. |
Prophylactic tranexamic acid in patients with hematologic malignancy: a placebo controlled, randomized clinical trial. Most common adverse events were: diarrhea [(116/164 (70.7%) TXA and 114/163 (69.9%) placebo)]; febrile neutropenia [111/164 (67.7%) TXA, 105/163 (64.4%) placebo]; fatigue [106/164 (64.6%) TXA, 109/163 (66.9%) placebo]; and nausea [104/164 (63.4%) TXA, 97/163 (59.5%) placebo]. Among patients with hematologic malignancy undergoing chemotherapy or hematopoietic stem cell transplantation, prophylactic treatment with tranexamic acid compared with placebo did not significantly reduce the risk of WHO grade 2 or higher bleeding. Trial Registration: Identifier: NCT02578901. |
Recurrent non-coding somatic and germline WT1 variants converge to disrupt MYB binding in acute promyelocytic leukemia. The high incidence of biallelic inactivation suggested the tumor suppressor activity of WT1 in APL. Mechanistically, non-coding WT1 variants disrupted MYB binding on chromatin and suppressed the enhancer activity and WT1 expression through destroying the chromatin looping formation. Our study highlights the essential role of non-coding variants in the leukemogenesis of APL. |
Role of Allogeneic Transplantation In Chronic Myelomonocytic Leukemia: An International Collaborative Analysis. In a multivariable analysis of lower-risk patients, performing allo-HCT before transformation to AML significantly increased the risk of death within two years of transplantation (HR=3.19, 95%CI 2.30-4.42, P<0.001), with no significant change in long-term survival beyond this time point (HR=0.98, 95%CI 0.58-1.64, P=0.92). In higher risk patients, allo-HCT significantly increased the risk of death in the first two years after transplant (HR=1.46, 95%CI 1.09-1.96, P=0.01), but not beyond (HR=0.60, 95%CI 0.34-1.08, P=0.09). Performing allo-HCT before AML transformation decreases life expectancy in lower risk patients but may be considered in higher risk patients. |
The genetic landscape of germline DDX41 variants predisposing to myeloid neoplasms. This superior OS was determined independent of blast count, abnormal karyotypes, and concurrent variants, including TP53 in AML/MDS patients, regardless of patient's sex, age or specific germline CV, suggesting that germline DDX41 variants define a distinct clinical entity. Furthermore, unrelated patients with myeloproliferative neoplasm (MPN) and B-cell lymphoma were linked by DDX41 CV, thus expanding the known disease spectrum. This study outlines the CV landscape, expands the phenotypic spectrum in unrelated DDX41-mutated patients, and underscores the urgent need for gene-specific diagnostic and clinical management guidelines. |
The Impact of T cell Immunity on Chemotherapy Response in Childhood Acute Lymphoblastic Leukemia. Consistent with these observations, IFNG and IL12 directly modulated dasatinib anti-leukemia efficacy in vivo. Finally, we evaluated peripheral blood immune cell composition in 102 children with ALL during chemotherapy and observed a significant association of T cell abundance with treatment outcomes. Together, these results suggest that T cell immunity plays pivotal roles in maintaining long-term remission of ALL, highlighting that the interplay between host immunity and drug resistance can be harnessed to improve ALL chemotherapy outcomes. |
The interaction between anti-PF4 antibodies and anticoagulants in vaccine-induced thrombotic thrombocytopenia. In contrast, argatroban showed no effect on procoagulant platelets and aggregation but significantly inhibited VITT-mediated thrombus formation. Taken together, our data indicate that negatively charged anticoagulants can disrupt VITT-Ab/PF4 interactions, which might serve as an approach to reduce Ab-mediated complications in VITT. Our results should be confirmed, however, in a clinical setting before a recommendation regarding the selection of anticoagulants in VITT patients could be made. |
Unique characteristics of lung resident neutrophils are maintained by PGE2/PKA/Tgm2-mediated signaling. Neutrophils from Tgm2-/- mice release high levels of inflammatory cytokines in response to LPS. Lung damage is significantly exacerbated in Tgm2-/- mice in an LPS-induced acute respiratory distress syndrome model. Collectively, we demonstrate that prostaglandin E2 is a key factor for the generation of LNs with unique immune suppressive characteristics, acting through protein kinase A and Tgm2, and LNs play essential roles in the protection of the lungs against pathogenic inflammation. |
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is mediated by a stereotyped clonotypic antibody. Moreover, striking stereotypic features were also identified in heavy-chains anti-PF4 antibodies characterised by identical HCDR3 length and homologous sequences. In summary, we unravelled the molecular signature of highly stereotyped clonotypic anti-PF4 antibodies, indicating shared pathways of antibody production in VITT patients. These discoveries are critical to understand the molecular basis of this serious condition and develop novel therapies aimed at removing pathogenic clones. |
| Blood Adv |
Amino acid stress response genes promote L-asparaginase resistance in pediatric acute lymphoblastic leukemia. SLC7A11 was also one of only 2.4% of LASP response genes with basal level gene expression that also correlated with LASP ex vivo resistance in primary leukemia cells. Experiments using chemical inhibition of SLC7A11 with sulfasalazine, gene overexpression, and partial gene knockout recapitulated LASP resistance or sensitivity in ALL cell lines. These findings show the importance of assessing changes in gene expression following treatment with an antileukemic agent for its association with drug resistance and highlight that many response genes may not differ in their basal expression in drug-resistant leukemia cells. |
Developing and validating a mortality prediction model for ICH in ITP: a nationwide representative multicenter study. Both calibration plots illustrated a high degree of consistency in the estimated and observed risk. In addition, the decision curve analysis showed a considerable net benefit for patients. Thus, an application (47.94.162.105:8080/ich/) was established for users to predict 30-day mortality when ICH occurred in adult patients with ITP. |
ETS1 is a novel transcriptional regulator of adult T-cell leukemia/lymphoma of North American descent. CCR4, a previously identified oncogenic factor in ATLL was found to be a direct ETS1 transcriptional target in NA-ATLL. As such, ETS1 provides an alternate mechanism to enhance CCR4 expression/activity in NA-ATLL, even in the absence of activating CCR4 mutations (CCR4 mutations were identified in 4 of 9 NA-ATLL cases). Taken together, this study identifies ETS1 as a novel dominant oncogenic transcriptional regulator in NA-ATLL. |
In vivo HSC transduction in rhesus macaques with an HDAd5/3+ vector targeting desmoglein 2 and transiently over-expressing cxcr4. In vivo transduction with a HDAd5/3+GFP/cxcr4 vector at a low dose of 0.4x1012vp/kg resulted in up to 7% of GFP-positive CD34+/CD45RA-/CD90+ cells in the bone marrow. This transduction rate is a solid basis for in vivo base or prime editing in combination with natural or drug-induced expansion of edited HSCs. Furthermore, our study provides new insights into HSC biology and trafficking after mobilization in non-human primates. |
Linked-read whole-genome sequencing resolves common and private structural variants in multiple myeloma. In addition, we identified private SVs causing the dysregulation of genes recurrently involved in translocations with the IGH locus and show that these can alter the molecular classification of the MM. Overall, we conclude that lrWGS allows for the detection of aberrations critical for MM prognostics and provides a feasible route for providing comprehensive genetics. Implementing lrWGS could provide more accurate clinical prognostics, facilitate genomic medicine initiatives, and greatly improve the stratification of patients included in clinical trials. |
Nurse-like cells sequester B cells in chronic lymphocytic leukemia disorganized lymph nodes via an alternative production of CCL21. Our results indicate NLCs as providers of an alternative source of CCL21, taking over the physiological task of follicular reticular cells (FRCs) whose network is deeply altered in CLL lymph nodes. Moreover, CCL21, by retaining malignant B cells, provide a protective environment for their niching and survival thus allowing immune tumor survey evasion and resistance to treatment. These findings argue for a specific targeting or re-education of NLCs as a new immunotherapy strategy for this still deadly disease. |
Ponatinib, Chemotherapy, and Transplant in Adults with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. The combination of chemotherapy with ponatinib followed by alloHSCT is well tolerated, with encouraging EFS in adults with newly diagnosed Ph+ALL. Cross-trial comparison suggests improvement versus imatinib. ( NCT02776605). |
Predicting major bleeding during extended anticoagulation for unprovoked or weakly provoked venous thromboembolism. Incidence of major bleeding events per 100 person-years in high- and non-high-risk patients, respectively, were 3.9 (95% confidence interval, 3.0-5.1) and 1.1 (0.8-1.4) using the newly derived CHAP model (creatinine, hemoglobin, age, and use of antiplatelet agent), 3.3 (2.6-4.1) and 1.0 (0.7-1.3) using modified ACCP, 5.3 (0.6-19.2) and 1.7 (1.4-2.0) using modified RIETE, 3.1 (2.3-3.9) and 1.1 (0.9-1.5) using modified VTE-BLEED, 5.2 (3.3-7.8) and 1.5 (1.2-1.8) using modified HAS-BLED, and 4.8 (1.3-12.4) and 1.7 (1.4-2.0) using modified OBRI scores. Modified versions of the ACCP, VTE-BLEED, and HAS-BLED scores help identify patients with unprovoked VTE who are at high risk of major bleeding and should be considered for discontinuation of anticoagulation after 3-6 months of initial treatment. The CHAP model may further improve estimation of bleeding risk by using continuous predictor variables, but external validation is required before its implementation in clinical practice. |
Prospective external validation of biomarkers to predict acute graft-versus host disease severity. In addition to clinical variables, biomarkers slightly improved the prediction of overall survival and NRM (concordance [C] and net reclassification indexes). The potential benefit of adding biomarkers panel to clinical parameters was also investigated by decision curve analyses. The benefit of adding biomarkers to clinical parameters was however marginal for the D28 non-response and mortality endpoints. |
PUM1 mediates the posttranscriptional regulation of human fetal hemoglobin. Knockdown of PUM1 leads to a robust increase in fetal hemoglobin (~22% HbF), without affecting ß-globin levels in human erythroid cells. Importantly, targeting PUM1 does not limit erythropoiesis progression, providing a potentially safe and effective treatment strategy in sickle cell anemia and ß-thalassemia. In support of this idea, we report elevated fetal hemoglobin levels in the absence of anemia, in an individual with a novel heterozygous PUM1 mutation in the RNA binding domain (p.(His1090Profs*16); c.3267_3270delTCAC), suggesting that PUM1 mediated post-transcriptional regulation is a critical player during human hemoglobin switching. |
Risk of diabetes and the impact on preexisting diabetes in lymphoma patients treated with steroid-containing immunochemotherapy. In a landmark analysis at one year, DM patients with lymphoma had decreased risks of insulin dependency compared to comparators. Time-varying IRRs showed a higher CVD risk for NHL patients with DM as compared to comparators in the first year after treatment. NHL patients treated with steroid-containing immunochemotherapy regimens have a clinically insignificant increased risk of DM in the first year following treatment, and patients with pre-existing DM have a temporary increased risk of insulin prescriptions and CVD. |
Single-cell spatial analysis of tumor immune architecture in diffuse large B-cell lymphoma. This is the first study to integrate tumor mutational profiling, cell of origin classification, and multiplexed immuno-phenotyping of the TME into a spatial analysis of DLBCL at the single cell level. We demonstrate that, far from being histo-pathologically monotonous, DLBCL has a complex tumor architecture, and that changes in tumor topology can be correlated with clinically relevant features. This analysis identifies candidate biomarkers and therapeutic targets such as TIM-3, CCR4, and CXCR3 that are relevant for combination treatment strategies in immuno-oncology and cellular therapies. |
Synonymous ADAMTS13 variants impact molecular characteristics and contribute to variability in active protein abundance. Using various prediction tools of biomolecular characteristics, we evaluated al ADAMTS13 sSNVs registered in the NCBI dbSNP, including 357 neutral sSNVs and 19 sSNVs identified in TTP patients. We showed that some sSNVs change mRNA folding energy/stability, disrupt mRNA splicing, disturb micro RNAs (miRNAs) binding sites, and alter synonymous codon or codon pair usage. Our findings highlight the importance of considering sSNVs when assessing the complex effects of ADAMTS13 alleles and our approach provides a generalizable framework to characterize sSNV impact in other genes and diseases. |
Upregulated SPAG6 promotes acute myeloid leukemia progression through MYO1D that regulates the EGFR family expression. Specifically, overexpression of SPAG6 promoted the translocation of MYO1D into the cell membrane, thus upgrading the expression level of the EGFR family and thereby promoting the progression of AML. Overall, our study found that SPAG6 combined with MYO1D and translocated MYO1D from the cytosol to the cytomembrane, which induced the PI3K/AKT signaling and ERK signaling pathway to regulate the growth and prognosis of AML. SPAG6 may become a new target gene for the treatment of AML. |
| Haematologica |
Characteristics and outcome of patients with acute myeloid leukemia and trisomy 4. An Andersen-Gill regression model on OS revealed ELN favorable-risk (HR, 0.34; P=0.006) and trisomy 4 as sole abnormality (HR, 0.41 P=0.01) as favorable factors, whereas age with a difference of ten years (HR, 1.15, P=0.11), female gender (OR, 0.74; P=0.20) and allo-HCT (OR, 0.64; P=0.14) had no significant impact. In our cohort, patients with trisomy 4 as a sole abnormality had a high CR rate and favorable clinical outcome. Allo-HCT seems not to improve OS. |
PET-imaging assessment for guiding strategy in patients with relapsed/refractory large B-cell lymphoma receiving CAR T-cells. Response at M3 evaluated in 90 (57%) patients was prognostic for PFS with lower discrimination (HR=3.28 (95%CI: 1.5-7.0), p=0.003) but did not predict OS (HR = 0.61 (95%CI: 0.2-2.3) p=0.45). Patients with high baseline total metabolic tumor volume (TMTV) >80ml had worse PFS (HR=2.05 (95%CI: 1.2-3.5), p=0.009) and OS (HR=4.52 (95%CI: 2.5-8.1), p80ml, and DS-5 at M1 for OS. In conclusion, baseline TMTV and response at M1 strongly predicts outcomes of patients with R/R LBCL undergoing CAR T-cells. |
| J Hematol Oncol |
| Lancet Haematol |
Activity and safety of topical pimecrolimus in patients with early stage mycosis fungoides (PimTo-MF): a single-arm, multicentre, phase 2 trial. Further controlled clinical trials are warranted to confirm these results. Funding Instituto de Salud Carlos III and the European Regional Development Fund. Translation For the Spanish translation of the abstract see Supplementary Materials section. |
| Leukemia |
CD147 a direct target of miR-146a supports energy metabolism and promotes tumor growth in ALK+ ALCL. Investigation of metabolism in vitro and in vivo supported these findings, revealing reduced aerobic glycolysis and increased basal respiration in CD147 knockdown. In conclusion, our findings indicate that CD147 is of vital importance for ALK+ ALCL to maintain the high energy demand of rapid cell proliferation, promoting lactate export, and tumor growth. Furthermore, CD147 has the potential to serve as a novel therapeutic target in ALK+ ALCL, and warrants further investigation. |
Evolution of eligibility criteria for non-transplant randomized controlled trials in adults with acute myeloid leukemia. A total of 27 eligibility criteria were used across trials, mostly concerning comorbidities or performance status, with eight of them becoming more common over time. The concordance with recent ASCO - Friends of Cancer Research eligibility criteria recommendations greatly varied, from 35% to 99%. Together, our analyses suggest that the ability to generalize results from non-transplant RCTs may be increasingly limited because of high non-enrollment rates and increasingly restrictive eligibility criteria. |
Histone demethylase KDM4C is a functional dependency in JAK2-mutated neoplasms. These findings led to reduced disease penetrance and improved survival in xenograft models of human JAK2-mutated cells. KDM4C deleted cells showed alterations in target histone residue methylation and target gene expression, resulting in induction of cellular senescence. In summary, these data establish KDM4C as a specific dependency and therapeutic target in JAK2-mutated cells that is essential for oncogenic signaling and prevents induction of senescence. |
Impact of BCR::ABL1 transcript type on RT-qPCR amplification performance and molecular response to therapy. This subtle difference led to measurable transcript-type dependent variation in estimates of residual disease which could be corrected by (i) taking the qPCR amplification efficiency into account, (ii) using alternative RT-qPCR approaches or (iii) droplet digital PCR (ddPCR), a technique which is relatively insensitive to differences in amplification kinetics. In CML patients, higher levels of BCR::ABL1/GUSB were identified at diagnosis for patients expressing e13a2 (n |
Novel mitochondria-targeting compounds selectively kill human leukemia cells. These compounds exhibited synergy with several anti-leukemia agents in AML, acute lymphoblastic leukemia (ALL), or chronic myelogenous leukemia (CML). Pilot in vivo efficacy studies indicate anti-leukemic efficacy in a MOLM14/GFP/LUC xenograft model, including extended survival in mice injected with leukemic cells pre-treated with PS127B or PS127E and in mice treated with PS127E at a dose of 5 |
| Thromb Haemost |
Point of Care Assessment of Direct Oral Anticoagulation in Acute Ischemic Stroke: Protocol for a Prospective Observational Diagnostic Accuracy Study. Viscoelastic point-of-care assessment of clotting time in whole blood might improve swift delivery of time-sensitive hyperacute treatment with IVT in stroke patients. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Blood |
| Blood Cancer J |
Resistance to targeted therapies: delving into FLT3 and IDH. Recent advances in FLT3 and IDH targeted inhibition have improved response rates and overall survival in patients with mutations affecting these respective proteins. Despite this success, resistance mechanisms have arisen including mutations that disrupt inhibitor-target interaction, mutations impacting alternate pathways, and changes in the microenvironment. Here we review the role of these proteins in leukemogenesis, their respective inhibitors, mechanisms of resistance, and briefly ongoing studies aimed at overcoming resistance. |
| CA Cancer J Clin |
Oncologic emergencies and urgencies: A comprehensive review. Emergent and urgent complications associated with targeted therapeutics, including small molecules, naked and drug-conjugated monoclonal antibodies, as well as immune checkpoint inhibitors and chimeric antigen receptor T-cells, are summarized. Finally, strategies for facilitating same-day direct admission to hospice from the ED are discussed. This article not only can serve as a point-of-care reference for the ED physician but also can assist outpatient oncologists as well as inpatient hospitalists in coordinating care around the ED visit. |
| J Hematol Oncol |
Clinical experiences with venetoclax and other pro-apoptotic agents in lymphoid malignancies: lessons from monotherapy and chemotherapy combination. Venetoclax is active in other lymphoid malignancies including several B cell non-Hodgkin lymphomas, acute lymphoblastic leukemia and multiple myeloma, with the highest intrinsic sensitivity observed in mantle cell lymphoma and Waldenstrom macroglobulinemia. Venetoclax combination with standard regimens in follicular lymphoma, multiple myeloma and aggressive B cell neoplasms has shown some promise, but further studies are required to optimize dose and scheduling to mitigate increased myelosuppression and infection risk, and to find validated biomarkers of venetoclax sensitivity. Future research will focus on overcoming venetoclax resistance, targeting other BCL2 family members and the rational design of synergistic combinations. |
How we treat NK/T-cell lymphomas. Autologous HSCT does not improve outcome. In relapsed/refractory cases, novel approaches comprise immune checkpoint blockade of PD1/PD-L1, EBV-specific cytotoxic T-cells, monoclonal antibodies, and histone deacetylase inhibitors. Future strategies may include inhibition of signalling pathways and driver mutations, and immunotherapy targeting the lymphoma and its microenvironment. |
Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape. Overall, elucidating the underlying mechanisms by which HIFs promote evasion of tumor immune surveillance will allow for targeting HIF in tumor treatment. This review discusses the current knowledge of how hypoxia and HIFs facilitate tumor immune escape, with evidence to date implicating HIF1A as a molecular target in such immune escape. This review provides further insight into the mechanism of tumor immune escape, and strategies for tumor immunotherapy are suggested. |
Patient selection for CAR T or BiTE therapy in multiple myeloma: Which treatment for each patient? Studies suggest that the early use of immunotherapy may improve outcomes significantly. In this review, we summarize the currently available clinical literature on CAR and BiTE in MM. Furthermore, we will compare these two T cell-based immunotherapies and discuss potential therapeutic approaches to promote development of new clinical trials, using T cell-based immunotherapies, even as bridging therapies to a transplant. |
| Lancet Haematol |
| Leukemia |
Maintenance therapy for acute lymphoblastic leukemia: basic science and clinical translations. Because of the large inter-individual variations in MTX/6-MP bioavailability and metabolism, dose adjustments are traditionally guided by the degree of myelosuppression, but this does not accurately reflect treatment intensity. DNA-TG is a common downstream metabolite of MTX/6-MP combination chemotherapy, and a higher level of DNA-TG has been associated with a lower relapse hazard, leading to the development of the Thiopurine Enhanced ALL Maintenance (TEAM) strategy-the addition of low-dose (2.5-12.5 |
Relapsed acute myeloid leukemia in children and adolescents: current treatment options and future strategies. Another major barrier to improvement in outcomes for relapsed pediatric AML is the historic lack of availability and participation in clinical trials. There are ongoing efforts to launch multinational clinical trials of emerging therapies. The purpose of this review is to summarize currently available and newly developed therapies for relapsed pediatric AML. |
Letters to the editors and authors’ replies
| Blood Cancer J |
| J Hematol Oncol |
DTX-P7, a peptide-drug conjugate, is highly effective for non-small cell lung cancer. More importantly, we found that DTX-P7 promoted cell cycle reentry of slow-proliferating CSLCs and subsequently killed them, exhibiting a "proliferate to kill" pattern. Collecitvely, by force of active targeting delivery of DTX via membrane-bound Hsp90, DTX-P7 induces unfolded protein response and subsequent apoptosis by degrading Hsp90, meanwhile awakens and kills the dormant cancer stem cells. Thus, DTX-P7 deserves further development as a promising anticancer therapeutic for treatment of various membrane-harboring Hsp90 cancer types. |
Mammary adipocytes protect triple-negative breast cancer cells from ferroptosis. Mechanistically, oleic acid secreted from adipocytes inhibited lipid peroxidation and ferroptosis of triple-negative breast cancer cells in the presence of ACSL3. Taken together, mammary adipocytes can protect breast cancer cells from ferroptosis through oleic acid in the presence of ACSL3. These findings could provide new ideas and targets for tumor treatment. |
| Lancet Haematol |
all remaining publications eg case reports, images of the month, etc…
| Blood |
| Blood Adv |
| Lancet Haematol |
| Leukemia |